AHCC^® Clinical Evidence

Japanese Journal of Clinical Oncology
Sumiyoshi Y, Hashine K, Kakehi Y, Yoshimura K, Satou T, Kuruma H, Namiki S, Shinohara N.
Dietary administration of mushroom mycelium extracts in patients with early stage prostate cancers
managed expectantly: a phase II study.
2010 Oct; 40(10): 967-72

Topic:
Does AHCC^® have an effect on patients with early stage prostate cancer?

Background:
Owing to widespread use of PSA screening, most prostate cancers are discovered at an extremely early stage. An alternative to active treatment, expectant management (also known as “watchful waiting”) has been adopted as a treatment for prostate cancer. This has resulted in interest of prostate patients in using complementary and alternative medicine, such as dietary supplements. Few clinical trials on dietary supplements on early stage prostate cancer have been conducted. AHCC^® has been reported to have immunestimulating activity, anti-cancer activity and cancerpreventative actions. What is its effect on early stage prostate cancer?

Study Type:
Human clinical intervention trial.

Study Design:
Open-label trial: Patients were treated with AHCC^® for 6 consecutive months, and for willing patients, the period was extended for an additional 6 months. A PSA test and biochemical examination were performed every 2 months. In addition, immune parameters such as T helper 1/T helper 2 ratio and NK cell activity were monitored. A questionnaire survey of the state-trait anxiety inventory (STAI) – a test for measuring anxiety – was given before treatment and after 6 months.

Subjects:
74 total: 40 prostate patients undergoing expectant management and 34 patients who had already undergone expectant management for 6 months or more.

Dosage:
4.5 grams of AHCC^® per day.

Results:
AHCC^® supplementation resulted in the following changes:

• Changes in PSA before and after treatment were substantially stable
• In patients for which expectant management had been continued for 6 months or more before the trial, a prolonged PSA doubling time (PSADT) was seen with AHCC^® administration
• Prior to AHCC^®, 12/31 (39%) of patients had PSADT of 120 months or more, and after 6 months of AHCC^® administration,
  17/31 (55%) had PSADT of 120 months or more
• To the lower end, 12/31 (39%) of patients showed a PSADT less than 24 months, and following 6 months of AHCC^®, this fell to 9/31 (29%)
• Anxiety significantly decreased after 6 months of treatment in patients exhibiting strong anxiety before the start of the trial

Conclusion:
“These results suggest that dietary uptake of AHCC^® contributes to the stabilization of the disease status in patients with
early stage prostate cancer who are expectantly managed.”

Anti-Cancer Drugs
Turner J, Chaudhary U. Dramatic prostate-specific antigen response with active hexose correlated compound in metastatic castrationresistant prostate cancer.
2009 Mar; 20(3): 215-216

Topic:
Does AHCC^® have an effect on castration-resistant prostate cancer (CRPC)?

Background:
Castration-resistant prostate cancer is defined as progression of disease with serum testosterone controlled below a castrate level. The median survival of patients CRPC is approximately 18 months. The use of herbal supplements in many malignancies has been increasing over the last several years. Previous research has shown that AHCC^® has activity in prostate cancer, ovarian cancer and multiplemyeloma. Will it be effective against CRPC?

Study Type:
Case study

Study Design:
A Caucasian male with CRPC with high-risk features who benefited less than 6 months from initial complete androgen blockade began self-administration of AHCC^®.

Subjects:
1 Caucasian male (66 years old) with CRPC

Dosage:
Not reported.

Results:
The self-administration of AHCC^® resulted in a dramatic PSA decrease within 1 month, which continued to control his disease for over 6 months from initial supplementation with AHCC^®.

Conclusion:
“Based on limited studies to date, it seems that AHCC^® may have a role in the management of prostate cancer patients, especially those who have failed hormonal therapy. Larger studies are equired to analyze the impact on this new therapy in prostate cancer patients.”

Journal of Hepatology
Matsui Y, Uhara J, Satoi S, Kaibori M, Yamada H, Kitade H, Imamura A, Takai S, Kawaguchi Y, Kwon AH, Kamiyama Y.
Improved prognosis of postoperative hepatocellular carcinoma patients when treated with functional foods:
a prospective cohort study.
2002 Jul; 37(1): 78-86

Topic:
Can AHCC^® improve the prognosis of hepatocellular carcinoma (HCC) patients following surgical treatment?

Background:
The prevention and treatment of the recurrence of hepatocellular carcinoma following hepatic resection has been studied extensively. However, the prognosis for HCC remains unsatisfactory, with the 5-year survival rate after primary surgical treatment at approximately 40% in Japan. There have been many attempts to treat the cancer by stimulating with biological response modifiers (BRMs), but the clinical efficacy of these substances has not been clearly confirmed. AHCC^® may be considered a potent BRM in the treatment of cancer patients.

Study Type:
Observational study.

Study Design:
Prospective cohort study: From February 1, 1992 to December 31, 2001, a total of 269 consecutive patients with istologically confirmed HCC were studied. All of the patients underwent resection of a liver tumor. The enrolled patients were addressed to each arm of the study based on their choice of the therapeutic options, and were trusted with the self-administration of AHCC^®. Researchers examined time to treatment failure (disease recurrence or death) and ten parameters related to liver function after surgery.

Subjects:
269 consecutive patients with histologically confirmed HCC.

Dosage:
3 grams of AHCC^® per day (n=113).

Results:
The AHCC^® group had the following significant differences compared with control group:
• Longer non-recurrence period • Increased overall survival rate

Conclusion:
“This study suggests that AHCC^® intake can improve the prognosis of postoperative HCC patients.

International Journal of Integrative Medicine
Ishizuka, R., et. al. Review of Cancer Therapy with Clinical Evidence and GCP®; The Long-Term Follow-Up Over 12 Years
For stage IV (M1) Cancer of the Lung and the Breast.
2010 July; vol. 2, no. 1

Topic:
Does AHCC^® in combination with GCP extend survival and quality of life in stage IV lung and breast cancer patients?

Background:
According to the domestic statistics on cancer death in 2006, lung cancer has been increasing and has the worst cancer mortality in Japan. Breast cancer has become the fourth-most-common cancer. AHCC^® from a specially fermented shiitake mushroom extract, and GCP (full name tK), which is derived from the isoflavone aglycone genistein from soybeans and combined with polysaccharides, when used together have augmented immune properties. They have both been used in individual evidence-based medicine for stage IV lung and breast cancer. This report does a long-term follow-up on these cases.

Study Type:
Observational study.

Study Design:
Retrospective cohort study: The subjects were breast and lung cancer patients who were treated with AHCC^® and GCP. Lung cancer patients had already undergone evidence-based chemotherapy; however, most of them discontinued or refused, owing
to its noneffect or side effects. Immunotherapy administering AHCC^® daily to the patients for nearly 2 weeks, coadministered with GCP, was conducted when their appetite and mental well-being were restored. The results were compared with the prognosis of breast cancer described in the investigation report of national breast cancer patient registration as a reference datum.

Subjects:
• 36 patients with stage IB-IV lung cancer.
• 34 patients with stage IV breast cancer.

Dosage:
• 2.25–4.5 grams of AHCC^®.
• 0.96–1.92 grams of GCP.

Results:
Compared with the survival rates in American Society of Clinical Oncology reference data, this retrospective study reported the following observations:
• 1-year, 2-year, and 3-year survival rates for stage IV lung cancer increased to 75.0%, 52.1%, and 21.8%, respectively.
4-year survival was 6.2%, and 5-year survival was 0%
• 41.7% of 36 M1 patients in classes A and B had improved quality of life (QOL)
• Improvement of 1-year to 3-year survival rates and prolongation of median survival time for stage IV lung cancer
• QOL scores of 35 cases were rated A to C by 77.2% of patients, which contributed to reducing final hospitalization time
• Survival terms for breast cancer patients for 1 year, 2 years, 3 years, 4 years, and 5 years were 100%, 84.4%, 68.3%, 36.8%, and 28.1%, respectively • Mean survival terms for breast cancer patients were 5 years, 2 months after recurrence and 7 years, 11 months after initial diagnosis
• Survival terms for breast cancer patients for 3 years, 4 years, and 5 years were 65.6%, 43.8%, and 28.1%, respectively
• Extension of survival terms was confirmed. • QOL scores improved 67.7%

Conclusion:
“AHCC^® and GCP could contribute to the extension of survival terms and improved QOL for patients on cancer therapy as compared to those using conventional therapy alone, according to clinical evidence-based medicine.”

Natural Medicine Journal
Kawaguchi, Y. Improved survival of patients with gastric cancer or colon cancer when treated with active hexose correlated compound (AHCC^®): effect of AHCC^® on digestive system cancer.
2009 September; 1(1): 1-6

Topic:
Does AHCC^® have an effect on the survival rate of patients with gastric cancer or colon cancer?

Background:
Gastric cancer is the second most common cause of cancer death and colorectal cancer is the third most commonly diagnosed cancer worldwide. Current treatment options include surgical resection and/or chemotherapy regimes. However, both forms of cancer have poor survival rates. The 5-year survival for patients with unresectable metastatic colon cancer is less than 10% and gastric cancer has an estimated age-adjusted survival rate of 33-44% in the United States and 51 – 54% in Japan. Tumor immunotherapy may provide another therapeutic option in an integrated approach. AHCC^® has demonstrated immune-stimulating activity and may be a potent biological response modifier (BRM) in cancer therapy

Study Type:
Observational study.

Study Design:
Prospective cohort study: Patients with a histopathological diagnosis of gastric or colon cancer were recruited to receive oral AHCC^® as a postoperative adjunctive therapy in conjunction with standard chemotherapy. The cumulative survival rates for gastric and colon cancer patients were analyzed by KaplanMeier method.

Subjects:
132 patients diagnosed with gastric cancer, 113 patients diagnosed with colon cancer

Dosage:
For stage I, II or III patients: 3 grams of AHCC^® per day (1 g three times per day. For stage IV patients: 6 grams of AHCC^® per day (2 g three times per day).

Results:
AHCC^® supplementation resulted in the following difference in survival rate:
• Improved cumulative 5-year survival rates for patients with gastric cancer (stage IA to stage IIIA) compared with other Japanese institutions
• Improved cumulative 5-year survival rates for patients with colon cancer (stage II to stage IIIA) compared with other Japanese institutions

Conclusion:
“AHCC^® is a potent BRM that may improve survival in patients with early stage gastric or colon cancer and warrants further investigation as an adjunctive immunotherapeutic in gastric and colon cancer treatment.”

Presented at the 40th APA (American Pancreatic Association), November 2009
Yanagimoto H, Satoi S, Toyokawa H, Yamamoto T, Hirooka S, Yamao J, Araki H, Matsui Y, Kwon A. The beneficial effect of active
hexose correlated compound (AHCC^®), a health food component, in patients with pancreatic or biliary tract cancer
who undergo chemotherapy

Topic:
Does AHCC^® have an effect on patients with pancreatic or biliary tract cancer who underwent chemotherapy?

Background:
AHCC^® has been previously shown to enhance immune function in healthy volunteers and to improve prognosis in hepatocellular carcinoma patients. Cancer chemotherapy is effective in many cases; however, it side effects can be severe. The effect of AHCC^® on chemother patients with pancreatic or biliary tract cancer.

Study Type:
Human clinical intervention trial.

Study Design:
Open-label, non-randomized phase II study: Researchers studied postoperative patients with histologically or cytologically proven adenocarcinoma of pancreas or biliary tract, who underwent chemotherapy with gemcitabine. Gemcitabine was given intravenously at a dose of 1,000 mg/mL once a week for 3 weeks, followed by 1 week of rest. Patients were divided into two groups, which were given AHCC^® (n=37) or nothing (n=38). The assessment of hematological and non-hematological toxicity was performed over 2 months during the chemotherapy

Subjects:
73 patients with PS of 0-1, and adequate organ function.

Dosage:
Not reported.

Results:
AHCC^® supplementation resulted in the following changes compared with the control group:
• The hemoglobin (Hb) level after chemotherapy in AHCC^® group was significantly higher
• The taste alteration after chemotherapy in AHCC^® group was significantly lower

Conclusion:
“It is suggested that AHCC^® could alleviate side effects of chemotherapy and that the nutritional state during chemotherapy might be maintained by improving the taste alteration. Further clinical trials will be necessary to clarify the beneficial effect of AHCC^®.”

International Journal of Clinical Medicine
arida D, Wakame K, Nomura T. Integrating complimentary and alternative medicine in the form of active hexose
correlated compound (AHCC^®) in the management of head & neck cancer patients.
2011, 2, 588-592

Topic:
Can AHCC^® be used in the treatment of head and neck cancer patients?

Background:
In the state of Meghalay, India, the incidence of cancer of the head and neck region is highest in males, while esophageal cancer is highest in females. This is directly correlated to the high use of tobacco.

Study Type:
Human clinical intervention trial.

Study Design:
Open-label trial: Patients were administered AHCC^® every morning 3 days prior to chemotherapy and followed up to
1 week post chemotherapy.

Subjects:
25 patients of advance state (T3-T4) head and neck cancer.

Dosage:
3 grams of AHCC^® per day

Results:
AHCC^® supplementation resulted in the following observations:
• All patients tolerated AHCC^® with no added symptoms
• 20 patients reported feeling better and stronger than before at the time of initiation of chemotherapy cycles
• Almost all patients reported better appetites after they started to take AHCC^®
• In 12 patients who required blood transfusions before chemotherapy cycles, a decrease in the rate of fall of hemoglobin
was observed and only 3 patients subsequently required blood transfusions prior to chemotherapy
• 22 patients has a reduction of chemotherapy side effects like nausea, vomiting, loose bowel movements/constipation, etc.
• Tumors regressed in 11 patients
• 8 patients stabilized

Conclusion:
“It can be concluded that AHCC^® is safe to administer and definitely helps cancer patients in reducing side effects of chemotherapy, improving sense of well-being and preparing them mentally and physically to continue and tolerate further chemotherapy cycles.

The Journal of Alternative and Complementary Medicine
Hangai, Sho, MD, et al. Effect of Active Hexose-Correlated Compound in Women Receiving Adjuvant Chemotherapy for Breast Cancer: A Retrospective Study.
2013 Nov; 19(11): 1–6

Topic:
What is the difference in chemotherapy treatment adverse effects and incidence in those receiving AHCC^® and those who didn’t?

Background:
First-line chemotherapy used in treating breast cancer includes the use of anthracyclines and taxanes, which are associated with significant toxicity and side effects, including nausea, vomiting, hair loss, bone marrow suppression, hepatotoxicity, and many others. Very severe side effects may result in discontinuation or delay of chemotherapy. Side effects reduce healthrelated quality of life, however, active hexose-correlated compound (AHCC^®) in rodents has reduced such chemotherapy side effects as bone marrow suppression, hepatotoxicity, and nephrotoxicity. In this study, side effects from chemotherapy of those taking AHCC^® versus those who didn’t were compared.

Study Type:
Human intervention, open-labeled, control study without placebo.

Study Design:
Forty-one women who were treated with anthracyclines and taxanes were selected for this study. Comparison was made of occurrence of adverse events in patients who received AHCC^® with those who did not receive AHCC^®. Using Fisher’s exact tests, the worstgrade adverse events in each treatment cycle were determined. Generalized use of granulocyte colonystimulating factor in the two groups was analyzed using Student’s t-test. The medical records of women treated for breast cancer were used to select female patients who fulfilled the following criteria: 1) were between the ages of 20 and 64; 2) had pathologically proven breast cancer; and 3) were receiving doxorubicin and cyclophosphamide (AC therapy), followed by taxanebased regimens. Patients who had taken AHCC^® during chemotherapy were analyzed as the AHCC^® group. Each patient in this group had taken a total of 1.0 g of AHCC^® orally after each meal. Patients who had not taken AHCC^® were analyzed as the control group.

Subjects:
41 women with breast cancer and using taxane or anthracyclines chemotherapy treatment.

Dosage:
1 gram.

Results:
It was found that compared with the control group, the AHCC^® group had significantly fewer neutrophilrelated events (odds ratio: 0.30; p = 0.016), significantly lower use of granulocyte colony-stimulating factor, and a higher (although not significant) rate of adverse events associated with c-glutamyl transpeptidase, a liver enzyme.

Conclusion:
AHCC^® has the potential to reduce the severity of neutropenia induced by breast cancer chemotherapy and the need to use granulocyte-CSF during chemotherapy as a remedial therapy. Overall data suggest that AHCC^® may reduce the toxicity of chemotherapy and may then allow for intensification of the chemotherapy dosage. A prospective trial is needed to study the effects of AHCC^® related to adverse events associated with c-GTP.

Biotherapy Jang Seok Won. The hematoimmunologic effect of AHCC^® for Korean patients with various cancers.
2002 November; 16(6): 560-564

Topic:
Does AHCC^® have a hematoimmunologic effect on cancer patients?

Background:
AHCC^® has immunomodulatory properties and is usually used as one of the complementary treatment agents for cancer patients. However, the mechanism of its antitumor effect is not clear.

Study Type:
Human clinical intervention trial.

Study Design:
Open-label trial: Patients were administered AHCC^® for 9 months. A peripheral blood examination, including total leukocytes, peripheral lymphocytes, hemoglobin and hematocrit (a measure of the proportion of blood occupied by red blood cells) was performed before AHCC^® administration and then every 3 months for a total of 3 times. Assessment of immune parameters was also performed before intake and then every 3 months after for a total of 2 times.

Subjects:
12 cancer patients.

Dosage:
3-6 grams of AHCC^® per day.

Results:
AHCC^® supplementation resulted in the following changes compared with baseline:
• The ratio of NK cells to total lymphocytes increased from 21.67% before taking AHCC^® to 26.21% and 26.0% 3 to 6
months after taking AHCC^®, respectively
• There was no change in white blood cells, hemoglobin, hematocrit and thrombocyte numbers after taking AHCC^®,
even though patients were undergoing radiotherapy or chemotherapy
• No adverse effects were observed

Conclusion:
“This study suggests that AHCC^® can be used for the prevention of bone marrow depression and chemotherapy.
Also, from the hematoimmunologic point of view, AHCC^® treatment seems to be safe and good for cancer patients,
acting as a biological response modifier.”

Reduction of Chemotherapy Side Effects

Topic:
Does AHCC^® have an immunomodulating effect on cancer patients?

Background:
AHCC^® is an enzyme-fermented extract of the basidiomycetes mushroom. The complex compound contains a mixture of polysaccharides, amino acids, lipids and minerals. The predominant components are oligosaccharides, totaling approximately 74% of the total dry weight. Of these, nearly 20% are partially acetylated α-1,4-glucans, which are believed to constitute the active compounds in AHCC^®.

Study Type:
Human clinical intervention trial.

Study Design:
Open-label trial: Cancer patients with different advanced malignancies participated in the study. Patients received AHCC^® for 2–6 months. NK cell activity was examined by 4-hour Cr release assay against sensitive K562 and resistant Raji tumor cells.

Subjects:
17 cancer patients.

Dosage:
3 grams of AHCC^® per day.

Results:
AHCC^® supplementation resulted in the following changes:
• Significant enhancement of NK activity against K562 as early as 2 weeks, two- to threefold increase compared with base line
• Activity was further increased at subsequent time periods up to 6 months post-treatment with AHCC^®
• NK activation was also detected against Raji cells, but at later stages 1-2 months with two- to ten fold increase compared with base line

Conclusion:
“We conclude that AHCC^® is a potent immunomodulator and may be useful in immunotherapy of cancer.”

The Medical News (Thailand)
Thaiudom S, Piyaniran W, Chutaputthi A. A study of the efficacy of active hexose correlated compound (AHCC^®) in the treatment of chronic hepatitis C patients at Phramongkutklao Hospital
(2010) 325, 13-16

Topic:
Does AHCC^® have an effect on patients with chronic hepatitis C?

Background:
Hepatitis C virus (HCV) infection is now a worldwide important issue with over 170 million people throughout the world have been infected with this virus. Generally, 2–35% of people infected with HCV will finally develop cirrhosis and hepatocellular carcinoma. The treatment for chronic hepatitis C patients causes many side effects and is also expensive. Previous research has shown that AHCC^® can increase numbers and function of several kinds of immune cells, while reducing HCV and ALT, a liver enzyme involved in the progression of hepatitis C. Can AHCC^® reduce HCV RNA levels and improve liver function?

Study Type:
Human clinical intervention trial.

Study Design:
Prospective, randomized, double-blind placebocontrolled trial: Patients received AHCC^® (n=19) or placebo (n=20) for 24 weeks. All patients received HCV RNA levels & liver function test monitoring. Also, the reduction of HCV RNA and ALT enzyme levels was observed. Patients who had not taken AHCC^® were analyzed as the control group.

Subjects:
39 chronic hepatitis C patients.

Dosage:
6 grams of AHCC^® per day.

Results:
AHCC^® supplementation resulted in the following changes:
• Although no significant reduction of HCV RNA levels was noticed in patients in the AHCC^® group compared to those in the placebo group, subgroup analysis of genotype-3 had a significant HCV RNA decline
• Although the reduction of ALT levels within AHCC^® group was not significant, a significant difference was found between AHCC^® and placebo groups
• The ALT levels were stable for the AHCC^® group, while ALT levels increased in the placebo group, and this difference was initially noted within the first six weeks of the study

Conclusion:
“Based on the result of this study, AHCC^® showed significant HCV RNA reduction in group B but not group A, and it could stabilize ALT levels when compared with placebo. This may delay the disease progression, providing patients more opportunities to receive any other treatment later on.”

Journal of Nutrition Science Vitaminology
Kim, Hyangkyoung, Jung-Ha Kim, and Jee-Aee Im. Effect of Active Hexose Correlated Compound (AHCC^®)
in Alcohol-Induced Liver Enzyme Elevation.
2014;60: 348–356

Topic:
What is the effect of Active Hexose Correlated Compound (AHCC^®) in alcohol-induced liver enzyme elevation?

Background:
The effect of AHCC^® supplementation and the mechanism of action of AHCC^® were tested in patients with alcohol-induced mildly elevated liver enzyme levels. AHCC^® is an enzyme-fermented extract of the shiitake mushroom available as a dietary supplement. The complex compound contains a mixture of polysaccharides, amino acids, lipids, and minerals. The predominant components are oligosaccharides, totaling approximately 71.2% of the total dry weight. This study was a randomized, controlled, double-blind clinical trial conducted at the Chung-Ang University Healthcare System in Seoul, South Korea.

Study Type:
Double-blind, randomized, placebo controlled human intervention trial (19 subjects in the placebo group, 21 in the 1-g AHCC^® group, 22 in the 3-g AHCC^® group).

Study Design:
Participants were randomly given either the placebo, 1 g of AHCC^®, or 3 g of AHCC^® and took the supplement for 12 weeks. Subjects visited the hospital for clinical and biochemical measurements, to report adverse events, return unused supplements, and to obtain their next supplements. Assessments included biochemical tests of liver enzymes, a questionnaire survey, and anthropometric measurements that were collected at the beginning and after every 4 weeks. Fatigue and mental stress was measured by reporting in the questionnaire. The brief fatigue inventory was composed of simple numeric rating scales from 0 to 10 for assessing fatigue. Severe fatigue was defined as a score of 7 or greater. For mental stress assessment, the Korean brief encounter psychosocial instrument (BEPSI-K), a validated indicator of perceived stress, was used. BEPSI-K consists of 5 items on a 1–5 Likert scale. A single observer performed anthropometric measurements in the morning after overnight fasting by the subjects, who wore light clothing and no shoes. A body composition analyzer (In body 3.0, Biospace, Seoul, South Korea) was used to measure their heights and body weights. The body mass index (BMI) was calculated by dividing the measured weight (kg) by the square of height (m2). Subjects sat on a chair in a stable and relaxed state, and their blood pressure was measured using a mercurial blood pressure tonometer. Each capsule was a light brown color and contained 167 mg of AHCC^® with 333 mg of dextrin and malt extract or a placebo of dextrin and malt extract. The treatment duration was set at 12 weeks since the effect of AHCC^® appeared after 3 months in a previous study. Patients were treated 30 minutes before breakfast and dinner for 12 weeks with 3 g/d AHCC^® (500 mg of AHCC^®/ capsule, 3 capsules × 2 doses) for the 3-g AHCC^® group, 1 g/d of AHCC^® (167 mg of AHCC^® with 333 mg of dextrin and malt extract/capsule). When the value of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) in the study period increased 2-fold or more compared with the base line or previous value, subjects were dropped from this study. The primary outcomes evaluated were the value and the percentage change of three liver enzymes (AST, ALT, and gamma-glutamyl transferase (g-GT)) in each group.

Subjects:
62 adults with elevated liver enzymes from alcohol consumptio

Dosage:
1 gram and 3 grams.

Results:
After 12 weeks of supplementation, the percentage change in alanine aminotransferase (ALT) levels was significantly different between the placebo and both AHCC^® groups (1 g of AHCC^® and 3 g of AHCC^®). Serum levels of tumor necrosis factor-α (p < 0.05) and interleukin-1β ( p < 0.01) were significantly lower, while those of adiponectin were higher in both AHCC^® groups than in the placebo group (p < 0.01). AHCC^® supplementation for 12 weeks may improve the levels of liver enzymes and circulating proinflammatory and anti-inflammatory cytokines in patients with alcohol-induced mildly elevated liver enzyme levels. The liver enzyme levels, lipid profiles, insulin resistance, and scores on fatigue and stress-related questionnaires did not show significant differences between the groups (p < 0.05); however, cytokine levels did show significant differences (TNF-α, IL-1β, and adiponectin, p < 0.05). Comparing the percentage changes at 12 weeks as analyzed by a paired t-test, a decrease in liver enzymes in both AHCC^® groups and a change in IL-1β and adiponectin in the 1-g AHCC^® group were found to be statistically significant. When analyzed with ANOVA, the percentage changes of serum levels of inflammatory cytokines, such as TNF-α (p < 0.05) and IL-1β (p < 0.01), were lower in the AHCC^® supplementation groups than in the placebo group. Serum levels of adiponectin were higher in both AHCC^® groups than in the placebo group (p < 0.05).

Conclusion:
Results demonstrated promising effects with a 12-week course of AHCC^® supplementation for improving liver enzyme levels and circulating proinflammatory and anti-inflammatory cytokines in patients with alcoholinduced liver enzyme elevation. AHCC^® supplementation for 12 weeks significantly improved ALT levels, decreased proinflammatory cytokines (TNF-α and IL-1β), and elevated anti-inflammatory cytokines (adiponectin) in both AHCC^® groups without any adverse events. Hepatoprotective effects accompanied by striking anti-inflammatory effects were observed regardless of the dosage.

11th International Conference of the Society for Integrative Oncology, Houston, TX, October 26–28, 2014
Evaluation of active hexose correlated compound (AHCC^®) for the Eradication of HPV Infections in Women with HPV positive Pap Smears. Smith, Judith A., Pharm.D., BCOP, CPHQ, FCCP, FISOPP, Jonathan Faro, M.D., Yu Bai, M.D., Barbara Rech, RN, Anjali Gaikwad, M.S., MB(ASCP), Joseph A. Lucci III, M.D., Joseph A. Rodriguez, M.D., Teresa T. Byrd, M.D

Topic:
Can women with HPV-positive Pap tests who don’t show signs of abnormal cytology (abnormal cervical cells) and are treated with active hexose correlated compound (AHCC^®) undergo clearance of the infection?

Background:
HPV DNA has been detected in over 99 percent of cervical cancer patients. HPV infection is one of the most important predisposing factors of cervical cancer, though not the only one. HPV appears to be an important cofactor in the development of dysplasia and cancer, but it does not cause either condition by itself. Smoking, drinking alcohol, and a poor diet may also be important cofactors. There is currently no known effective medicine or supplement for eradication of HPV infections. Previously completed preclinical in vitro and in vivo mouse data that suggested AHCC^® will eradicate HPV in 16 out of 18 infections attributed this to the modulation of the expression and signaling of interferon alpha and beta. It was suggested that AHCC^® may help prevent subsequent HPV-related cervical cancers. The virus infects epithelial and mucosal surfaces and is a very common viral infection — 230 subtypes of HPV have been identified, including 100 human subtypes. Fifteen of the human HPV subtypes are carcinogenic and include the common subtypes: HPV 16, 18, 31, 39, and 41. According to the U.S. Centers for Disease Control and Prevention, several other cancers are related to HPV through sexual transmission, including 95 percent of anal cancer, 60 percent of oropharyngeal cancer, 65 percent of vaginal cancer, 50 percent of vulvar cancer, and 35 percent of penile cancer. The primary objective of the pilot study was to confirm the preclinical findings to determine if AHCC^® is effective in eradicating HPV infections in women with negative-oncology Pap tests. AHCC^® is available over the counter as a nutritional supplement that functions by improving the innate immune system. Human and preclinical studies have shown that AHCC^® increases the number and/or activity of natural killer cells, dendritic cells, and cytokines. These help the body fight off infections, including those caused by viruses, and
help block tumor growth

Study Type:
Human intervention dose-finding pilot study

Study Design:
Case studies involving HPV-positive women treated orally with the extract AHCC^® once daily for up to 6 months. Patients who had documented persistent HPV-positive infections for greater than 2 years but were otherwise healthy and met the remaining eligibility criteria were enrolled in the study to evaluate the effectiveness of 3 g of AHCC^® by oral administration to eradicate HPV. The regimen was repeated every month until the patient tested HPV negative or until 3 months of active treatment had elapsed. Patients who tested positive after 6 months of treatment were considered treatment failures. HPV testing was completed with the Cervista® HPV HR Test (Hologic Inc., Bedford, MA) once a month, and a 2 mL blood sample was drawn for research purposes to monitor immune markers for response.

Subjects:
10 women with HPV-positive status.

Dosage:
3 grams, once a day on an empty stomach.

Results:
Five subjects achieved a negative HPV test result — three with confirmed eradication after stopping AHCC^® — with the remaining two responders continuing on the study.

Conclusion:
“The preliminary results from this pilot study confirm previous preclinical findings that AHCC^® appears to be effective for elimination of HPV infections. These results will justify further reinvestigation. A formal phase II randomized, placebo-controlled study is underway at UTHealth–University of Texas Medical School at Houston.”

Presented at the 22nd International Congress on Nutrition and Integrative Medicine (ICNIM), July 2014
Mikhailichenko, N. Estimating efficacy of AHCC^® as immune therapy for patients diagnosed with pharmacoresistant epilepsy.

Topic:
What effect does active hexose correlated compound (AHCC^®) supplementation have in patients diagnosed with pharmacoresistant epilepsy, to what degree is there a role in the immune system disease pathogenesis, and what is the efficacy of immune therapy?

Background:
Evidence of interaction between epilepsy and immunologic disorders has been growing over the last several decades. Clinical syndromes of secondary immunodeficiency have been found in 70–80 percent of cases involving mental patients with various severities of illness. Immunologic mechanisms may play a significant role in an integrated theory of epilepsy, and since infectious diseases such as ARVI, ENT diseases, urinary tract infections, and herpetic infections often attack patients with epilepsy, immune-correcting drugs have become a basis for treating these types of psychoimmunoneurological diseases. This study examined patients diagnosed with pharmacoresistant epilepsy and evaluated the effect of an immune-system role in pathogenesis of the disease and the efficacy of immune therapy using AHCC^® as a dietary supplement

Study Type:
Human clinical intervention trial

Study Design:
Case studies of several children with pharmacoresistant epilepsy were examined using clinical methods. Immunologic tests were performed to assess clinical syndromes of secondary immunodeficiency and to identify multiple defects in the immune system. Immunologic examination was performed according to standard methods. Immune status was measured by percentage of T- and B lymphocytes in peripheral blood (total number of lymphocytes, percentage and absolute number of mature T cells ( CD3+), T helpers (CD4+), and T killer-suppressors (CD8+), B lymphocytes (CD20+), and immunoregulatory balance between CD4+ and CD8+ concentrations. In addition, serum immunoglobulin A, G, and M (IgA, IgG, and IgM) were measured. All patients received combined treatment including base line antiepileptic and immune therapy using AHCC^®-2 for 1 month.

Subjects:
Several children.

Dosage:
Not reported.

Results:
Children with pharmacoresistant epilepsy had decreased mature T lymphocytes (CD3+) and T cells and an imbalance in the subset. The amount of CD3+ T lymphocytes in the epilepsy group was 42.42%±14.65%, which is 82.8% of average. The amount of CD4+ T lymphocytes was 71.6%, and cytotoxic CD8+ was 112.7%. The CD4+/CD8+ lymphocytes subset distribution and regulatory balance had a ratio of 1.28±0.55, which was below average or only 58.6% of the average value. After AHCC^® intake, patients had positive changes of peripheral T cell pool (CD3+) and T-helpers (CD4+). They also showed an improvement and increase in the ratio of T suppressors-killers (CD8+) to lymphocytes to 1.4. Due to increases in the CD4+ lymphocytes subset, the immunoregulatory balance of the CD4+ to CD8+ ratio improved. There was a 35% decrease of frequency and intensity of epileptic seizures. The patients’ bodily health status and physiological functions also improved.

Conclusion:
Patients with pharmacoresistant epilepsy have been found to have significant neuroimmune disorders, according to the results of immune cell testing. AHCC^® immunotherapy improves immune status by increasing the amount of T lymphocytes, by regulating the subset balance, and by activating phagocytes and humoral function. In addition, AHCC^® treatment decreased neurological immune dysfunction by regulating the amount of serum immunoglobulins, indicating a reversal of the autoimmune process that has significance in the development of epilepsy.